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george daley

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https://www.readbyqxmd.com/read/29625070/a-clk3-hmga2-alternative-splicing-axis-impacts-human-hematopoietic-stem-cell-molecular-identity-throughout-development
#1
Marcella Cesana, Michael H Guo, Davide Cacchiarelli, Lara Wahlster, Jessica Barragan, Sergei Doulatov, Linda T Vo, Beatrice Salvatori, Cole Trapnell, Kendell Clement, Patrick Cahan, Kaloyan M Tsanov, Patricia M Sousa, Barbara Tazon-Vega, Adriano Bolondi, Federico M Giorgi, Andrea Califano, John L Rinn, Alexander Meissner, Joel N Hirschhorn, George Q Daley
While gene expression dynamics have been extensively cataloged during hematopoietic differentiation in the adult, less is known about transcriptome diversity of human hematopoietic stem cells (HSCs) during development. To characterize transcriptional and post-transcriptional changes in HSCs during development, we leveraged high-throughput genomic approaches to profile miRNAs, lincRNAs, and mRNAs. Our findings indicate that HSCs manifest distinct alternative splicing patterns in key hematopoietic regulators...
April 5, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29567829/the-pancreatic-cancer-microbiome-promotes-oncogenesis-by-induction-of-innate-and-adaptive-immune-suppression
#2
Smruti Pushalkar, Mautin Hundeyin, Donnele Daley, Constantinos P Zambirinis, Emma Kurz, Ankita Mishra, Navyatha Mohan, Berk Aykut, Mykhaylo Usyk, Luisana E Torres, Gregor Werba, Kevin Zhang, Yuqi Guo, Qianhao Li, Neha Akkad, Sarah Lall, Benjamin Wadowski, Johana Gutierrez, Juan Andres Kochen Rossi, Jeremy W Herzog, Brian Diskin, Alejandro Torres-Hernandez, Josh Leinwand, Wei Wang, Pardeep S Taunk, Shivraj Savadkar, Malvin Janal, Anjana Saxena, Xin Li, Deirdre Cohen, R Balfour Sartor, Deepak Saxena, George Miller
We found that the cancerous pancreas harbors a markedly more abundant microbiome compared with normal pancreas in both mice and humans, and select bacteria are differentially increased in the tumorous pancreas compared with gut. Ablation of the microbiome protects against preinvasive and invasive pancreatic ductal adenocarcinoma (PDA), whereas transfer of bacteria from PDA-bearing hosts, but not controls, reverses tumor protection. Bacterial ablation was associated with immunogenic reprogramming of the PDA tumor microenvironment, including a reduction in myeloid-derived suppressor cells and an increase in M1 macrophage differentiation, promoting TH1 differentiation of CD4+ T cells and CD8+ T-cell activation...
April 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29497036/reconstruction-of-complex-single-cell-trajectories-using-cellrouter
#3
Edroaldo Lummertz da Rocha, R Grant Rowe, Vanessa Lundin, Mohan Malleshaiah, Deepak Kumar Jha, Carlos R Rambo, Hu Li, Trista E North, James J Collins, George Q Daley
A better understanding of the cell-fate transitions that occur in complex cellular ecosystems in normal development and disease could inform cell engineering efforts and lead to improved therapies. However, a major challenge is to simultaneously identify new cell states, and their transitions, to elucidate the gene expression dynamics governing cell-type diversification. Here, we present CellRouter, a multifaceted single-cell analysis platform that identifies complex cell-state transition trajectories by using flow networks to explore the subpopulation structure of multi-dimensional, single-cell omics data...
March 1, 2018: Nature Communications
https://www.readbyqxmd.com/read/29342143/regulation-of-embryonic-haematopoietic-multipotency-by-ezh1
#4
Linda T Vo, Melissa A Kinney, Xin Liu, Yuannyu Zhang, Jessica Barragan, Patricia M Sousa, Deepak K Jha, Areum Han, Marcella Cesana, Zhen Shao, Trista E North, Stuart H Orkin, Sergei Doulatov, Jian Xu, George Q Daley
All haematopoietic cell lineages that circulate in the blood of adult mammals derive from multipotent haematopoietic stem cells (HSCs). By contrast, in the blood of mammalian embryos, lineage-restricted progenitors arise first, independently of HSCs, which only emerge later in gestation. As best defined in the mouse, 'primitive' progenitors first appear in the yolk sac at 7.5 days post-coitum. Subsequently, erythroid-myeloid progenitors that express fetal haemoglobin, as well as fetal lymphoid progenitors, develop in the yolk sac and the embryo proper, but these cells lack HSC potential...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29325868/a-canadian-genome-wide-association-study-and-meta-analysis-confirm-hla-as-a-risk-factor-for-peanut-allergy-independent-of-asthma
#5
Yuka Asai, Aida Eslami, C Dorien van Ginkel, Loubna Akhabir, Ming Wan, David Yin, George Ellis, Moshe Ben-Shoshan, Ingo Marenholz, David Martino, Manuel A Ferreira, Katrina Allen, Bruce Mazer, Hans de Groot, Nicolette W de Jong, Roy Gerth van Wijk, Anthony E J Dubois, Sarah Grosche, Sarah Ashley, Franz Rüschendorf, Birgit Kalb, Kirsten Beyer, Markus M Nöthen, Young-Ae Lee, Rick Chin, Stephen Cheuk, Joshua Hoffman, Eric Jorgensen, John S Witte, Ronald B Melles, Xiumei Hong, Xiaobin Wang, Jennie Hui, Arthur W Bill Musk, Michael Hunter, Alan L James, Gerard H Koppelman, Andrew J Sandford, Ann E Clarke, Denise Daley
No abstract text is available yet for this article.
April 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29273806/multiancestry-association-study-identifies-new-asthma-risk-loci-that-colocalize-with-immune-cell-enhancer-marks
#6
Florence Demenais, Patricia Margaritte-Jeannin, Kathleen C Barnes, William O C Cookson, Janine Altmüller, Wei Ang, R Graham Barr, Terri H Beaty, Allan B Becker, John Beilby, Hans Bisgaard, Unnur Steina Bjornsdottir, Eugene Bleecker, Klaus Bønnelykke, Dorret I Boomsma, Emmanuelle Bouzigon, Christopher E Brightling, Myriam Brossard, Guy G Brusselle, Esteban Burchard, Kristin M Burkart, Andrew Bush, Moira Chan-Yeung, Kian Fan Chung, Alexessander Couto Alves, John A Curtin, Adnan Custovic, Denise Daley, Johan C de Jongste, Blanca E Del-Rio-Navarro, Kathleen M Donohue, Liesbeth Duijts, Celeste Eng, Johan G Eriksson, Martin Farrall, Yuliya Fedorova, Bjarke Feenstra, Manuel A Ferreira, Maxim B Freidin, Zofia Gajdos, Jim Gauderman, Ulrike Gehring, Frank Geller, Jon Genuneit, Sina A Gharib, Frank Gilliland, Raquel Granell, Penelope E Graves, Daniel F Gudbjartsson, Tari Haahtela, Susan R Heckbert, Dick Heederik, Joachim Heinrich, Markku Heliövaara, John Henderson, Blanca E Himes, Hiroshi Hirose, Joel N Hirschhorn, Albert Hofman, Patrick Holt, Jouke Hottenga, Thomas J Hudson, Jennie Hui, Medea Imboden, Vladimir Ivanov, Vincent W V Jaddoe, Alan James, Christer Janson, Marjo-Riitta Jarvelin, Deborah Jarvis, Graham Jones, Ingileif Jonsdottir, Pekka Jousilahti, Michael Kabesch, Mika Kähönen, David B Kantor, Alexandra S Karunas, Elza Khusnutdinova, Gerard H Koppelman, Anita L Kozyrskyj, Eskil Kreiner, Michiaki Kubo, Rajesh Kumar, Ashish Kumar, Mikko Kuokkanen, Lies Lahousse, Tarja Laitinen, Catherine Laprise, Mark Lathrop, Susanne Lau, Young-Ae Lee, Terho Lehtimäki, Sébastien Letort, Albert M Levin, Guo Li, Liming Liang, Laura R Loehr, Stephanie J London, Daan W Loth, Ani Manichaikul, Ingo Marenholz, Fernando J Martinez, Melanie C Matheson, Rasika A Mathias, Kenji Matsumoto, Hamdi Mbarek, Wendy L McArdle, Mads Melbye, Erik Melén, Deborah Meyers, Sven Michel, Hamida Mohamdi, Arthur W Musk, Rachel A Myers, Maartje A E Nieuwenhuis, Emiko Noguchi, George T O'Connor, Ludmila M Ogorodova, Cameron D Palmer, Aarno Palotie, Julie E Park, Craig E Pennell, Göran Pershagen, Alexey Polonikov, Dirkje S Postma, Nicole Probst-Hensch, Valery P Puzyrev, Benjamin A Raby, Olli T Raitakari, Adaikalavan Ramasamy, Stephen S Rich, Colin F Robertson, Isabelle Romieu, Muhammad T Salam, Veikko Salomaa, Vivi Schlünssen, Robert Scott, Polina A Selivanova, Torben Sigsgaard, Angela Simpson, Valérie Siroux, Lewis J Smith, Maria Solodilova, Marie Standl, Kari Stefansson, David P Strachan, Bruno H Stricker, Atsushi Takahashi, Philip J Thompson, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Carla M T Tiesler, Dara G Torgerson, Tatsuhiko Tsunoda, André G Uitterlinden, Ralf J P van der Valk, Amaury Vaysse, Sailaja Vedantam, Andrea von Berg, Erika von Mutius, Judith M Vonk, Johannes Waage, Nick J Wareham, Scott T Weiss, Wendy B White, Magnus Wickman, Elisabeth Widén, Gonneke Willemsen, L Keoki Williams, Inge M Wouters, James J Yang, Jing Hua Zhao, Miriam F Moffatt, Carole Ober, Dan L Nicolae
We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases...
January 2018: Nature Genetics
https://www.readbyqxmd.com/read/29212039/comprehensive-mapping-of-pluripotent-stem-cell-metabolism-using-dynamic-genome-scale-network-modeling
#7
Sriram Chandrasekaran, Jin Zhang, Zhen Sun, Li Zhang, Christian A Ross, Yu-Chung Huang, John M Asara, Hu Li, George Q Daley, James J Collins
Metabolism is an emerging stem cell hallmark tied to cell fate, pluripotency, and self-renewal, yet systems-level understanding of stem cell metabolism has been limited by the lack of genome-scale network models. Here, we develop a systems approach to integrate time-course metabolomics data with a computational model of metabolism to analyze the metabolic state of naive and primed murine pluripotent stem cells. Using this approach, we find that one-carbon metabolism involving phosphoglycerate dehydrogenase, folate synthesis, and nucleotide synthesis is a key pathway that differs between the two states, resulting in differential sensitivity to anti-folates...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29069550/is-there-merit-in-merit-aid
#8
Roy C Ziegelstein, Charles G Prober, Lloyd B Minor, George Q Daley, Paul B Rothman, Edward M Hundert
In 2016, the average cost of attending medical school (including tuition and fees) in the United States was $253,720 for in-state graduates and $313,897 for out-of-state graduates. Nearly three in four graduates had educational debt, and the median educational debt was $190,000. Average debt..
December 21, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29030101/genome-wide-association-study-and-meta-analysis-in-multiple-populations-identifies-new-loci-for-peanut-allergy-and-establishes-c11orf30-emsy-as-a-genetic-risk-factor-for-food-allergy
#9
Yuka Asai, Aida Eslami, C Dorien van Ginkel, Loubna Akhabir, Ming Wan, George Ellis, Moshe Ben-Shoshan, David Martino, Manuel A Ferreira, Katrina Allen, Bruce Mazer, Hans de Groot, Nicolette W de Jong, Roy N Gerth van Wijk, Anthony E J Dubois, Rick Chin, Stephen Cheuk, Joshua Hoffman, Eric Jorgensen, John S Witte, Ronald B Melles, Xiumei Hong, Xiaobin Wang, Jennie Hui, Arthur W Bill Musk, Michael Hunter, Alan L James, Gerard H Koppelman, Andrew J Sandford, Ann E Clarke, Denise Daley
BACKGROUND: Peanut allergy (PA) is a complex disease with both environmental and genetic risk factors. Previously, PA loci were identified in filaggrin (FLG) and HLA in candidate gene studies, and loci in HLA were identified in a genome-wide association study and meta-analysis. OBJECTIVE: We sought to investigate genetic susceptibility to PA. METHODS: Eight hundred fifty cases and 926 hyper-control subjects and more than 7.8 million genotyped and imputed single nucleotide polymorphisms (SNPs) were analyzed in a genome-wide association study to identify susceptibility variants for PA in the Canadian population...
March 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28928278/an-interview-with-george-daley
#10
Aidan Maartens
George Daley is Dean of the Faculty of Medicine, Professor of Biological Chemistry and Molecular Pharmacology, and Caroline Shields Walker Professor of Medicine at Harvard Medical School. A former Howard Hughes Medical Institute Investigator and President of the International Society for Stem Cell Research (ISSCR) from 2007-2008, his lab works on the biology and clinical application of stem cells, with a particular focus on hematopoiesis. He was awarded the Public Service Award at the ISSCR 2017 meeting in Boston, where we caught up with him to discuss his move from the lab to the clinic and back again, his quest to derive human hematopoietic stem cells in vitro , and his advocacy for science in uncertain political times...
September 15, 2017: Development
https://www.readbyqxmd.com/read/28686862/making-hscs-on-demand-looking-ahead
#11
(no author information available yet)
George Daley and Shahin Rafii's groups recently generated multilineage, serially engrafting hematopoietic stem cells (HSCs) from human pluripotent stem cells and endothelial cells, respectively, achieving an important research milestone for the field. We asked some experts in the field to reflect on the broader implications of these findings.
July 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28619647/using-crispr-cas9-to-generate-gene-corrected-autologous-ipscs-for-the-treatment-of-inherited-retinal-degeneration
#12
Erin R Burnight, Manav Gupta, Luke A Wiley, Kristin R Anfinson, Audrey Tran, Robinson Triboulet, Jeremy M Hoffmann, Darcey L Klaahsen, Jeaneen L Andorf, Chunhua Jiao, Elliott H Sohn, Malavika K Adur, Jason W Ross, Robert F Mullins, George Q Daley, Thorsten M Schlaeger, Edwin M Stone, Budd A Tucker
Patient-derived induced pluripotent stem cells (iPSCs) hold great promise for autologous cell replacement. However, for many inherited diseases, treatment will likely require genetic repair pre-transplantation. Genome editing technologies are useful for this application. The purpose of this study was to develop CRISPR-Cas9-mediated genome editing strategies to target and correct the three most common types of disease-causing variants in patient-derived iPSCs: (1) exonic, (2) deep intronic, and (3) dominant gain of function...
September 6, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28531208/phylogenetic-analysis-of-emergent-streptococcus-pneumoniae-serotype-22f-causing-invasive-pneumococcal-disease-using-whole-genome-sequencing
#13
Walter H B Demczuk, Irene Martin, Linda Hoang, Paul Van Caeseele, Brigitte Lefebvre, Greg Horsman, David Haldane, Jonathan Gubbay, Sam Ratnam, Gregory German, Jennifer Daley Bernier, Lori Strudwick, Allison McGeer, George G Zhanel, Gary Van Domselaar, Morag Graham, Michael R Mulvey
Since implementation of the 13-valent polyvalent conjugate vaccine (PCV13) in Canada during 2010, the proportion of PCV13 serotypes causing invasive pneumococcal disease (IPD) has declined from 55% (n = 1492) in 2010 to 31% (n = 764) in 2014. A concurrent increase of non-PCV13 serotypes has occurred and 22F has become the most prevalent serotype in Canada increasing from 7% (n = 183) to 11% (n = 283). Core single nucleotide variant phylogenetic analysis was performed on 137 Streptococcus pneumoniae serotype 22F isolates collected across Canada from 2005-2015...
2017: PloS One
https://www.readbyqxmd.com/read/28514439/haematopoietic-stem-and-progenitor-cells-from-human-pluripotent-stem-cells
#14
Ryohichi Sugimura, Deepak Kumar Jha, Areum Han, Clara Soria-Valles, Edroaldo Lummertz da Rocha, Yi-Fen Lu, Jeremy A Goettel, Erik Serrao, R Grant Rowe, Mohan Malleshaiah, Irene Wong, Patricia Sousa, Ted N Zhu, Andrea Ditadi, Gordon Keller, Alan N Engelman, Scott B Snapper, Sergei Doulatov, George Q Daley
A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts...
May 25, 2017: Nature
https://www.readbyqxmd.com/read/28442553/nlrp3-signaling-drives-macrophage-induced-adaptive-immune-suppression-in-pancreatic-carcinoma
#15
Donnele Daley, Vishnu R Mani, Navyatha Mohan, Neha Akkad, Gautam S D Balasubramania Pandian, Shivraj Savadkar, Ki Buom Lee, Alejandro Torres-Hernandez, Berk Aykut, Brian Diskin, Wei Wang, Mohammad S Farooq, Arif I Mahmud, Gregor Werba, Eduardo J Morales, Sarah Lall, Benjamin J Wadowski, Amanda G Rubin, Matthew E Berman, Rajkishen Narayanan, Mautin Hundeyin, George Miller
The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance, which enables disease to progress unabated by adaptive immunity. However, the drivers of this tolerogenic program are incompletely defined. In this study, we found that NLRP3 promotes expansion of immune-suppressive macrophages in PDA. NLRP3 signaling in macrophages drives the differentiation of CD4+ T cells into tumor-promoting T helper type 2 cell (Th2 cell), Th17 cell, and regulatory T cell populations while suppressing Th1 cell polarization and cytotoxic CD8+ T cell activation...
June 5, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28429768/reassembling-embryos-in-vitro-from-component-stem-cells
#16
Caroline Kubaczka, George Q Daley
Researchers at the University of Cambridge, UK have succeeded in reconstructing mouse embryos by combining pluripotent embryonic and multipotent trophoblast stem cells in a 3D scaffold; the study from the laboratory of Professor Zernicka-Goetz, recently published in Science, provides a break-through tool to probe early mammalian development outside the uterus. Achieving a similar feat with human cells might necessitate reconsideration of the 14-day rule as a limitation of such research.
August 2017: Cell Research
https://www.readbyqxmd.com/read/28394331/dectin-1-activation-on-macrophages-by-galectin-9-promotes-pancreatic-carcinoma-and-peritumoral-immune-tolerance
#17
Donnele Daley, Vishnu R Mani, Navyatha Mohan, Neha Akkad, Atsuo Ochi, Daniel W Heindel, Ki Buom Lee, Constantinos P Zambirinis, Gautam Sd Balasubramania Pandian, Shivraj Savadkar, Alejandro Torres-Hernandez, Shruti Nayak, Ding Wang, Mautin Hundeyin, Brian Diskin, Berk Aykut, Gregor Werba, Rocky M Barilla, Robert Rodriguez, Steven Chang, Lawrence Gardner, Lara K Mahal, Beatrix Ueberheide, George Miller
The progression of pancreatic oncogenesis requires immune-suppressive inflammation in cooperation with oncogenic mutations. However, the drivers of intratumoral immune tolerance are uncertain. Dectin 1 is an innate immune receptor crucial for anti-fungal immunity, but its role in sterile inflammation and oncogenesis has not been well defined. Furthermore, non-pathogen-derived ligands for dectin 1 have not been characterized. We found that dectin 1 is highly expressed on macrophages in pancreatic ductal adenocarcinoma (PDA)...
May 2017: Nature Medicine
https://www.readbyqxmd.com/read/28350984/autophagy-it-s-in-your-blood
#18
COMMENT
Sergei Doulatov, George Q Daley
Autophagy, a central pathway for cellular homeostasis, plays diverse roles in development, cancer, aging, and neurodegeneration. In a new report in Nature, Ho et al. (2017) show that autophagy is essential for maintaining the replicative quiescence of hematopoietic stem cells throughout life by limiting the number of active mitochondria.
March 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28345379/the-role-of-%C3%AE-%C3%AE-t-cells-in-pancreatic-cancer-what-could-this-mean-for-the-clinic
#19
Donnele Daley, George Miller
No abstract text is available yet for this article.
April 11, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28296612/polar-extremes-in-the-clinical-use-of-stem-cells
#20
George Q Daley
The U.S. biotechnology and pharmaceutical industries arguably lead the world in innovation while operating under stringent regulations set by the Food and Drug Administration (FDA). Although flexible pathways exist to accelerate the development or approval of treatments for serious illnesses or..
March 16, 2017: New England Journal of Medicine
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